ACTIVITIES OF CLARITHROMYCIN, AZITHROMYCIN, AND OFLOXACIN IN COMBINATION WITH LIPOSOMAL OR UNENCAPSULATED GRANULOCYTE-MACROPHAGE COLONY-STIMULATING FACTOR AGAINST INTRAMACROPHAGE MYCOBACTERIUM-AVIUM MYCOBACTERIUM-INTRACELLULARE

The effects of ofloxacin, clarithromycin, and azithromycin in combinat ion with granulocyte-macrophage colony-stimulating factor (GM-CSF) aga inst Mycobacterium avium-Mycobacterium intracellulare (MAI) were evalu ated in an in vitro human macrophage infection model. Treatment of MAI -infected macrophages with GM-CSF alone induced a maximal killing effe ct at 1000 U/mL, and the potency was increased 100-fold by encapsulati ng the cytokine within liposomes. Antibiotics were applied at concentr ations close to their clinically achievable serum trough and peak leve ls. Addition of GM-CSF to azithromycin and therapeutic trough concentr ations of ofloxacin and clarithromycin was associated with significant (P < .01) augmentation of antimycobacterial activity compared with th e effects of the agents alone. However, the enhancement effect by GM-C SF was not seen with therapeutic peak concentrations of ofloxacin and clarithromycin. Thus, GM-CSF may be a useful adjunct in the treatment of MAI infections with azithromycin, clarithromycin, and ofloxacin.